Rheumatology 2001; 40: 707-709
© 2001 British Society for Rheumatology
Letters to the Editor |
A severe case of acquired hypophosphataemic osteomalacia: the perils of a missed diagnosis
Department of Bone and Mineral Metabolism and
1 Department of Morbid Anatomy, Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, Middlesex HA7 4LP, UK
SIR, A 61-yr-old man presented to his general practitioner (GP) in August 1990 with a 3-yr history of progressive bony pain and difficulty in walking. In January 1990 he had sustained a low trauma fracture of the left hip and, despite surgical repair, had remained wheelchair-bound. He was referred to a rheumatologist and subsequently to a neurologist, but no organic cause for his symptoms was found. In late 1997, because of persistent complaints of bone pain to his GP, he was referred to our department.
On examination he was unable to bear weight unaided. There was gross truncal deformity with severe kyphoscoliosis. The right hip was shortened and externally rotated. He was centrally cyanosed and tachypnoeic. There was a large, irregular soft tissue mass in the upper right arm.
Investigations revealed normal urea and electrolytes, full blood count, transaminases and 
-glutamyl transferase. Arterial blood gases showed severe type 2 respiratory failure, and spirometry confirmed a marked restrictive pattern. Serum corrected calcium was 2.48 mmol/l (normal range 2.10–2.70), serum phosphate 0.31 mmol/l (0.70–1.5), serum alkaline phosphatase 340 U/l (30–130), 25-hydroxyvitamin D 67 nmol/l (20–195), 1,25-hydroxyvitamin D 23 pg/l (25–150), parathyroid hormone (PTH) 187 pg/ml (12–72), 24-h urinary phosphorous excretion 12.1 mmol (16–48), and tubular resorption of phosphorus 68% (85–95).
Plain X-ray skeletal survey showed changes compatible with a diffuse osteomalacia, and magnetic resonance imaging (MRI) scan of the soft tissue mass was performed. Morphological features of the soft tissue mass in the upper arm were difficult to classify but were consistent with a low-grade sarcoma (Fig. 1
). A needle iliac crest bone biopsy confirmed gross osteomalacia (Fig. 2).
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A diagnosis of oncogenic osteomalacia secondary to a probable low-grade sarcoma was made. Surgical debulking of the tumour under regional blockade was undertaken, tissue from which is growing well in culture and producing a putative phosphaturic substance (P. Rowe, Royal Free Hospital, personal communication). Following a single fraction of local radiotherapy, our patient was treated with calcitriol initially at a dose of 6 µg/day, Ossopan granules 6 g/day and phosphate-Sandoz three tablets/day. Nocturnal nasal ventilation, in the form of variable positive airway pressure support, together with domiciliary oxygen has been successful in improving his gaseous exchange. He remains a high anaesthetic risk and it is unlikely that he will be suitable at any stage for repair of the fractured right femoral neck; his rehabilitation will be limited by this and his poor ventilatory function.
To date there has been prompt normalization of serum phosphate accompanied by a gradual rise in serum-corrected calcium concentration to supranormal levels, with persistently high serum PTH. Urinary calcium excretion is low, suggesting tertiary hyperparathyroidism. Clinically, there has been a marked objective improvement in muscle strength and he is now able to bear weight unaided.
Adult-onset osteomalacia secondary to increased renal phosphate clearance may be associated with benign tumours of mesenchymal origin. Resection of the primary tumour commonly effects a cure [1], yet failure to establish a clear diagnosis or identify the tumour deprives many patients of this early, potentially definitive procedure. Misdiagnoses of skeletal metastases and Paget's disease have been described ([2], G. Clunie et al., personal communication). The variable nomenclature ascribed to the histological appearance of the tumours associated with renal phosphate wasting reflects the wide morphological spectrum that is seen [1]. The most commonly identified is that of the haemangiopericytoma. The pathophysiology of oncogenic hypophosphataemic osteomalacia (OHO) remains the subject of investigation, but two candidate proteins have recently been isolated from cultured tumour cells of patients with OHO that in vitro alter sodium-dependent phosphate cotransport and 1-
hydroxylase activity [3]. Reports suggest that complete tumour resection, combined initially with large doses of calcitriol, phosphate and calcium supplements, results in a cure in the majority of patients. However, tumours may be occult and if they are not apparent on thorough clinical examination detailed imaging in the form of total body computed tomography or MRI is probably justified.
Medical treatment alone in those patients in whom tumour cannot be identified appears to be sufficient to effect bony healing and clinical recovery, but treatment in such cases will necessarily be lifelong. Long-term follow-up is necessary even in those patients in whom tumour resection has been deemed complete, as recurrence may occur many years later. The appearance of tertiary hyperparathyroidism in OHO during the early treatment phase, as occurred in our patient, has been reported to occur in approximately 5% of patients [4].
In conclusion, OHO is a rare but potentially devastating condition. Our patient's diagnosis, in common with many others described in the literature, did not come to light until over a decade after the onset of symptoms. Thus, a degree of astuteness is required in order to avoid failure of recognition. While there have been reports of patients presenting with late features, such as immobility, most present with bone pain, pseudofractures and/or a waddling gait. To our knowledge this is the first reported case manifesting such a devastating complication as severe respiratory failure secondary to extensive truncal collapse, as well as wheelchair confinement.
Notes
Correspondence to: J. R. MacGowan, Department of Rheumatology, Watford General Hospital, Vicarage Road, Watford WD1 8HB, UK. 
References
- Ryan EA, Reiss E. Oncogenous osteomalacia. Review of the world literature of 42 cases and report of two new cases. Am J Med1984;77:501–12.[Medline]
- O'Donnell D, Meyers AM. Hypophosphataemic osteomalacia misdiagnosed as metastatic carcinoma. A case report. S Afr Med J1998;67:934–5.
- Rowe PS, Ong AC, Cockerill FJ, Goulding JN, Hewison M. Candidate 56 and 58 kDa protein(s) responsible for mediating the renal defects in oncogenic hypophosphatemic osteomalacia. Bone1996;18:159–69.[Medline]
- Olefsky J, Kempson R, Jones H et al. ‘Tertiary’ hyperparathyroidism after apparent ‘cure’ of vitamin-D resistant rickets after removal of an ossifying mesenchymal tumor of the pharynx. N Engl J Med1972;286:740–5.
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